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tional in children and should prompt detailed consideration of alternative diagnoses.4245 About 80% of pediatric
cases, and nearly all adolescent onset cases, present with
attacks typical for adult CIS, with a similar or greater total
T2 lesion burden.4648 In children younger than 11 years,
lesions are larger and more ill-defined than in teenagers.49
Imaging criteria for demonstrating DIS in pediatric MS
show high sensitivity and/or specificity.38,50,51
The Panels consensus was that the proposed MAGNIMS-based MRI revisions for DIS will also serve well
for most pediatric MS patients, especially those with acute
demyelination presenting as CIS, because most pediatric
patients will have >2 lesions and are very likely to have
lesions in 2 of the 4 specified CNS locations (periventricular, brainstem-infratentorial, juxtacortical, or spinal cord).
The frequency of spinal cord lesions in pediatric MS
patients is currently unreported, but the appearance of
cord lesions in pediatric MS patients with spinal cord
symptoms appears generally similar to that of adults.52
However, approximately 15 to 20% of pediatric
MS patients, most aged <11 years, present with encephalopathy and multifocal neurological deficits difficult
to distinguish from acute disseminated encephalomyelitis
(ADEM).43,50 Current operational international consensus criteria for MS diagnosis in children with an ADEMlike first attack require confirmation by 2 or more nonADEM like attacks, or 1 non-ADEM attack followed by
accrual of clinically silent lesions.53 Although children
with an ADEM-like first MS attack are more likely
than children with monophasic ADEM to have 1 or
more non-enhancing T1 hypointense lesions, 2 or more
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Future Directions
POTENTIAL ADDED VALUE OF BIOMARKERS. Although increased IgG index or the presence of oligoclonal
bands in the CSF support an MS diagnosis, and AQP4
antibody assays can help in the differential diagnosis process, there are still no specific biomarkers to confirm the diagnosis. Several blood and CSF biomarkers may be promising,6265 and high-resolution spectral domain optical
coherence tomography might be as good as VEP in assessing visual involvement.66 The diagnostic utility of such
markers needs to be validated and tested prospectively.
Clinical Presentation
Nonec
If the Criteria are fulfilled and there is no better explanation for the clinical presentation, the diagnosis is MS; if suspicious, but
the Criteria are not completely met, the diagnosis is possible MS; if another diagnosis arises during the evaluation that better
explains the clinical presentation, then the diagnosis is not MS.
a
An attack (relapse; exacerbation) is defined as patient-reported or objectively observed events typical of an acute inflammatory
demyelinating event in the CNS, current or historical, with duration of at least 24 hours, in the absence of fever or infection. It
should be documented by contemporaneous neurological examination, but some historical events with symptoms and evolution
characteristic for MS, but for which no objective neurological findings are documented, can provide reasonable evidence of a prior
demyelinating event. Reports of paroxysmal symptoms (historical or current) should, however, consist of multiple episodes occurring over not less than 24 hours. Before a definite diagnosis of MS can be made, at least 1 attack must be corroborated by findings
on neurological examination, visual evoked potential response in patients reporting prior visual disturbance, or MRI consistent
with demyelination in the area of the CNS implicated in the historical report of neurological symptoms.
b
Clinical diagnosis based on objective clinical findings for 2 attacks is most secure. Reasonable historical evidence for 1 past attack,
in the absence of documented objective neurological findings, can include historical events with symptoms and evolution characteristics for a prior inflammatory demyelinating event; at least 1 attack, however, must be supported by objective findings.
c
No additional tests are required. However, it is desirable that any diagnosis of MS be made with access to imaging based on these
Criteria. If imaging or other tests (for instance, CSF) are undertaken and are negative, extreme caution needs to be taken before
making a diagnosis of MS, and alternative diagnoses must be considered. There must be no better explanation for the clinical presentation, and objective evidence must be present to support a diagnosis of MS.
d
Gadolinium-enhancing lesions are not required; symptomatic lesions are excluded from consideration in subjects with brainstem
or spinal cord syndromes.
MS multiple sclerosis; CNS central nervous system; MRI magnetic resonance imaging; DIS dissemination in space; DIT
dissemination in time; PPMS primary progressive multiple sclerosis; CSF cerebrospinal fluid; IgG immunoglobulin G.
February 2011
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Acknowledgment
The work of the Panel was supported by the US
National Multiple Sclerosis Society (NMSS), the European Committee for Treatment and Research in Multiple
Sclerosis, the Multiple Sclerosis International Federation,
and MS Ireland.
The Panel thanks Drs T. Saida, M. Lana-Peixoto,
D. Callegaro, and C. Oehninger for help in gaining perspective on the use of the McDonald Criteria in Asia
and Latin America.
This work is dedicated to the memory of Dr W.
Ian McDonald, who chaired the original Panel and
whose continuing inspiration has driven the work for the
second and third revisions to the Criteria that now bear
his name.
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